Cerebrovascular Involvement in Liposome-Induced Cardiopulmonary Distress in Pigs

Intravenous administration of liposomes, including Doxil, can cause severe life-threatening hemodynamic changes in pigs. The reaction is due to complement activation, and it is characterized by massive pulmonary hypertension, systemic hypotension, and severe cardiac abnormalities including falling c...

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Bibliographic Details
Published in:Journal of liposome research 2005, Vol.15 (1-2), p.3-14
Main Authors: Bodo, Michael, Szebeni, Janos, Baranyi, Lajos, Savay, Sandor, Pearce, Frederick J., Alving, Carl R., Bünger, Rolf
Format: Article
Language:English
Subjects:
cerebrovascular reactivity
complement activation
liposome
rheoencephalogram
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Summary:Intravenous administration of liposomes, including Doxil, can cause severe life-threatening hemodynamic changes in pigs. The reaction is due to complement activation, and it is characterized by massive pulmonary hypertension, systemic hypotension, and severe cardiac abnormalities including falling cardiac output, tachy-or bradycardia with arrhythmia. There were no data suggesting the involvement of cerebrovascular changes in this reaction; however, clinical observations allowed this hypothesis. Here we measured the accompanying changes during liposome infusion by monitoring pulsatile electrical impedance (rheoencephalogram- REG) on the skull (n = 24 pigs, 57 trials, 19 types of liposomes). A transient but significant decrease of REG pulse amplitudes followed the injection of liposomes (78.43% in the total sample, and 91.66% in the Doxil subgroup; P = 0.003, n = 12), indicating the involvement of cerebrovascular reaction during liposome infusion.
ISSN:0898-2104
1532-2394
DOI:10.1081/LPR-64523